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Biomedical subjects

R W Morris

Publications and source records attributed to R W Morris.

At least 19 recordsLinked to original sources

p53 expression and prognosis in gastric carcinoma.

Abnormalities of the p53 gene have been identified in many malignancies, with reports of aberration in over half of colorectal, lung, breast and hepatocellular carcinoma cases. The normal gene acts as a recessive oncogene, while mutations change the apparent function to that of a dominant oncogene. In this investigation a 3-layered immunoperoxidase technique was applied to routinely fixed and paraffin-embedded tissue sections from 125 gastric carcinomas, using a polyclonal anti-p53 antibody (CM-I). We found that 57% of these carcinomas expressed high levels of p53 protein (positive nuclear staining). Survival analysis revealed a strong association between p53 status of the tumour and patient survival time after diagnosis (p = 0.02, Mantel-Cox Test); odds ratio of death, 2.09 (95% confidence interval 1.02 to 4.25). The 5-year survival of patients with p53-expressing tumours was 24%, compared with 56% for those non-p53-expressing tumours (the median survival times were 13 and 102 months, respectively).

Biomarkers, Tumor

Cutaneous responses to vasoactive intestinal polypeptide in chronic idiopathic urticaria.

Cutaneous wheal and flare responses to increasing concentrations of calcitonin gene-related peptide, substance P, neurokinin A, vasoactive intestinal polypeptide (VIP), compound 48/80, and phosphate-buffered saline were measured in 10 patients with chronic idiopathic urticaria and 10 healthy controls. A significant increase in VIP-induced wheal, but not flare or cutaneous blood flow, was seen in urticarial patients compared with controls (p less than 0.001). No significant differences in responses to other tested compounds were found between these groups. These data point to an increased sensitivity of microvasculature to VIP in patients with chronic idiopathic urticaria.

Adult

Measurement of cell proliferation in gastric carcinoma: comparative analysis of Ki-67 and proliferative cell nuclear antigen (PCNA).

Immunostaining to identify nuclear antigens expressed throughout the cell cycle provides a convenient way of assessing proliferating kinetics in tumours. We studied proliferation activity of gastric carcinomas by Ki-67 and PCNA immunostaining and the two methods were compared. The mode of tissue preparation differed, fresh frozen for Ki-67 and formalin-fixed paraffin-embedded for PCNA. Immunostaining with avidin-biotin was used in both. The labelling index (LI) and a semi-quantitative grading of cell proliferation were assessed in both markers. Significant correlation was shown between LI and grading with either Ki-67 and PCNA. However, no correlation was found between PCNA and Ki-67. This lack of relationship between the two markers may be attributed to a number of factors. 1. The most likely is the marked inter- and intra-tumour heterogeneity of gastric carcinomas reflected in high standard deviation values. 2. Preparation of tissue and small size sampling with Ki-67. 3. Long life of PCNA leading to detection of cells that have recently left the cell cycle. 4. One may be observing deregulated expression of DNA as seen in certain tumours. PCNA offers the advantage of being applicable to archival material.

Analysis of Variance

Occlusal adjustment therapy for craniomandibular disorders: a clinical assessment by a double-blind method.

Fifty-one patients with craniomandibular disorders were divided in two groups. One group underwent mock occlusal adjustment, the other was treated with adjustments to remove significant slides and non-working side interferences. Both groups received identical counseling. The results show that there was no significant difference in the improvements on the signs and symptoms obtained by real or mock adjustments after the first treatment session.

Adolescent

Cell proliferation study on gastric carcinoma and non-involved gastric mucosa using a bromodeoxyuridine (BrdU) labelling technique.

Previous reports using [3H]thymidine have shown altered patterns of cell proliferation in gastric carcinogenesis. In this study we applied in vitro bromodeoxyuridine (BrdU) uptake and immunohistochemistry to tissue from carcinoma, its adjacent mucosa and distant mucosa (n = 16) cases and 10 normal control cases. The labelling index (LI) was calculated for the upper, neck/isthmus and lower gland compartments and in 10 random fields/carcinoma. The LI was greater in the carcinoma than in either the adjacent or far mucosa or the controls (p < 0.001). No difference was observed between the non-carcinoma areas. However, the LI varied significantly between the gland compartments within each area (p < 0.001). In the normal control cases, the location of the proliferating cells was limited to the neck/isthmus region and perhaps the most significant observation was the change of location and expansion of the proliferative zone towards the surface in the normal mucosa adjacent to carcinoma compared with distant mucosa and controls (p < 0.001). These altered patterns of cell proliferation may be an important aspect of the precancerous potential of field changes in gastric carcinoma patients and could help patient follow-up and serve as a marker in monitoring intervention studies.

Bromodeoxyuridine

Anaesthetic experience with cryotherapy for treatment of hepatic malignancy.

Hepatic cryotherapy is a relatively new technique, currently employed in the treatment of unresectable liver malignancy, which involves direct freezing of tumour deposits with liquid nitrogen. In a review of 26 patients undergoing this procedure, the anaesthetic considerations are defined. The total operation time ranged from 133 to 410 minutes. In spite of preventative measures, varying degrees of hypothermia occurred (range 33.7 degrees C to 36.5 degrees C), but no sequelae were encountered. Mean blood loss was 926 ml, and eleven patients required blood transfusion of between one and five units. There was a marked drop in platelet count associated with cryotherapy (mean fall of 123,000/mm3 by the second postoperative day). Following the procedure, fever and basal pulmonary atelectasis were common, while hypoglycaemia and renal impairment occurred on single occasions. Six patients underwent postoperative mechanical ventilation. Despite this, the mean hospital stay was under seven days.

Adult

Periodicity of presentations of drugs of abuse and overdose in an emergency department.

In order to determine whether temporal factors impact on drugs of abuse and overdose presentations to an urban emergency department, we studied the records of 630 consecutive drug overdose presentations over a period from October 1987 to March 1990. Particular note was made of the time of day of presentation along with the nature of the drug(s) ingested. A significant curve (p less than 0.0005) was obtained for a 24 h period with a peak time of presentation being 6:32 pm (95% confidence interval of 1 h 54 min). Significant periodic rhythms were noted for cocaine, opiates, alcohol, analgesics, marijuana, and benzodiazepines. A 4.8 h periodic rhythm was demonstrated for cocaine, marijuana and alcohol-in-combination. We conclude that the emergency department should be most prepared to treat the drug overdose patient in the early evening and emergency department staffing should reflect this peak in demand.

Alcoholism

Evaluation of a rapid diagnostic test for group A beta-haemolytic streptococcus in general practice.

OBJECTIVE: to assess the efficacy of Abbott Testpack Strep A compared with throat culture for the diagnosis of group A beta-haemolytic streptococcus in general practice. METHODS: one hundred and fifty-four specimens were obtained from general practices in selected regions, and were tested for group A beta-haemolytic streptococcus using both Abbott Testpack Strep A and throat culture. RESULTS: sensitivity of the rapid diagnostic test was 79.4%, specificity 93.3%. The negative predictive value of the test was 94.1%; the positive predictive value 77.1%. CONCLUSION: maximum cost effectiveness is achieved, with respect to short term costs and benefits, by diagnosing and treating solely on the basis of Abbott Testpack Strep A results. When possible complications are taken into consideration, initial testing by Abbott Testpack Strep A, followed by confirmatory laboratory testing of negative Testpack results becomes a feasible alternative.

Bacteriological Techniques

c-erbB-2 proto-oncogene expression and its relationship to survival in gastric carcinoma: an immunohistochemical study on archival material.

The c-erbB-2 proto-oncogene encodes a growth factor receptor which is over-expressed in a variety of human adenocarcinomas. Recent reports suggest that it may be of value in arriving at prognosis in breast and ovarian cancer. In this study, c-erbB-2 expression was investigated in 93 routinely processed cases of gastric carcinoma, using an immunohistochemical technique. c-erbB-2 membrane immunoreactivity was observed in 11% (10/93) of tumours, all of which were of the well differentiated intestinal type (p less than 0.01). Overall, patients with tumours expressing this proto-oncogene had a significantly improved prognosis (p less than 0.05). Within the group of intestinal-type tumours, those that were c-erbB-2-positive formed a distinct sub-population which had a better prognosis (p less than 0.02), suggesting possible differences in aetiology.

Biomarkers, Tumor

Is DNA ploidy and proliferative activity of prognostic value in advanced gastric carcinoma?

We analyzed the DNA content of 116 gastric carcinomas and lymph node metastasis in 53 of these using flow cytometry on archival material. DNA index and proliferative activity (% S-phase) values were obtained in 111 and 76 tumors, respectively, and survival rates were obtained for 108. Tumor classification was based on histologic type, grade, and growth pattern and stage. All were advanced gastric carcinomas. Fifty four tumors (47%) were aneuploid. In single variable analysis, survival was related to stage (muscularis propria versus serosa P = .002) and lymph node metastasis (P = .04). Infiltrative tumor growth had a slightly worse prognosis (P = .06). In multifactorial analysis, tumor stage was the only independent prognostic factor. Neither DNA ploidy nor % S-phase values had any effect on survival, although, patients with tumors with higher DNA indexes (greater than 1.7) showed a tendency toward worse survival rates. We failed to prove the prognostic value of DNA ploidy in gastric carcinoma. Before its effect is ruled out, some factors have to be considered: (1) all tumors were in advanced stage and the true effect of ploidy on survival may have been diluted, (2) quality of fixation--near diploid aneuploid populations may have been overlooked, and (3) intratumoral DNA ploidy heterogeneity can cause sample discrepancy (20% in our series).

Adenocarcinoma

Do intensive care nurses consider intensive care less useful than their patients or patient's family?

Do Intensive Care Nurses feel that Intensive Care (IC) treatment is worthwhile for their patients? Can they speak for their patients, when considering how useful IC would be, in the event of life-threatening illness? And, do quality of life (QOL) considerations affect IC nurses', and patients', and patients' family perceptions of the usefulness of IC treatment? To determine how useful they perceived IC treatment to be 44 ex-patients (or their family if the patient had died) were asked how willing they would be to return to IC (or have their relative return to IC) if again threatened by critical illness. 16 Registered Nurses (RNs) were asked how useful they considered IC would be for patients they had nursed, if those patients' treatment in IC could be done all over again. RNs were also asked how useful they considered IC to be if they themselves required it. Patient (or family) responses were matched with the corresponding RN responses and compared (39 matched pairs). The comparison showed, 1--Patients and families did not consider QOL effected their judgement of the usefulness of IC; 2--Patients and families considered IC useful for all periods of survival; 3--RNs considered IC much less useful than patients and families; 4--QOL was a significant consideration for RNs when assessing the usefulness of IC for their patients. These results have implications for RNs who attempt to represent the patients' view when assessing the usefulness of IC.

Attitude of Health Personnel

Comparison of the real-time use of glycosylated haemoglobin and plasma fructosamine in the diabetic clinic.

The within-clinic use of glycosylated haemoglobin (HbA1) and plasma fructosamine results in assessing blood glucose control and clinical management was compared in 1030 diabetic patients. The physician initially reviewed the patient with one randomly allocated measure (HbA1 or fructosamine) and completed a questionnaire concerning perception of blood glucose control, alteration to diet, alteration to medication, referral for diabetes education, and follow-up interval. The patient was then re-assessed using the second measure and the questionnaire repeated. Discordance rates for the study end-points, judged as binary outcomes, were: blood glucose control 15%; alteration to diet 7%; alteration to medication 9%; referral for education 3%; follow-up interval 4%. A significantly greater number of patients were rated as poorly controlled with HbA1 than with fructosamine (p less than 0.001) and were, in consequence, more frequently recommended alteration to diet and medication, referral for education and shorter follow-up interval; the rate of discordance for at least one of the management decisions was 16%. Multifactorial analysis showed that discordant management was dependent on the reviewing physician (p less than 0.001) and a history of cardiovascular disease (p less than 0.01); but neither type of diabetes, nor presence of nephropathy or variant haemoglobins, nor plasma glucose concentration, significantly influenced the likelihood of a discordance. Replacing HbA1 with fructosamine in the diabetic clinic may result in significant differences in the physician's perception of blood glucose control and in the management of patients.

Adult

Audit from preschool developmental surveillance of vision, hearing, and language referrals.

Referrals from preschool medical examinations were followed up for two years to assess attendance rate, waiting time for appointment, appropriateness of the referral, the diagnosis and management of the condition. Altogether 184 children were referrals for ophthalmology, 285 for audiology, and 195 for speech therapy. The median waiting time for an appointment was 46 days in ophthalmology, 175 days in audiology, and 83 days in speech therapy. The poorest attendance rate was identified in speech therapy (75%). Approximately 60% of examined children had a justified referral to ophthalmology and 20% had a clear defect. Over half the children in audiology (55%) had an altered impedance or hearing impairment. Of those with a hearing problem kept under review only half improved spontaneously. In speech therapy 80% of those assessed had a language problem. Many health problems were detected for which parents were unaware or did not use the service. Parental awareness alone will not uncover the sizable level of lingual and sensorial problems in inner city areas. This audit identified specific deficiencies in the provision of services and a number of organisational changes are suggested to improve their effectiveness.

Age Factors

A graded combination regimen for maintenance of gastric pH above 3.5 in critically ill patients.

Prophylaxis of acute upper gastrointestinal bleeding by control of gastric pH has been widely advocated for intensive care patients. H2-blockers and antacids have been used and demonstrated to be incompletely effective at maintaining gastric pH above 4. A study of 100 patients measured the efficacy of two-hourly gastric pH measurement and titrated therapy consisting of five levels: 1. no therapy 2. ranitidine 50 mg 8 hourly intravenously 3. ranitidine plus Mylanta 30 ml 2 hourly by nasogastric tube 4. ranitidine plus Mylanta 60 ml 2 hourly and 5. ranitidine 100 mg 8 hourly intravenously plus Mylanta II 60 ml 2 hourly. The level of treatment required by proportions of the total study group were (1) 15%, (2) 71%, (3) 96%, (4) 100%. Head-injured and intubated patients generally fell in the more resistant group while patients having had major elective surgery required lower levels of therapy. If control of gastric pH is to be uniformly achieved, a technique of titrated therapy based on gastric pH measurements is supported as cheaper and more effective than other standardised treatment regimens.

Adult

Coronal alignment after total knee replacement.

Maquet's line passes from the centre of the femoral head to the centre of the body of the talus. The distance of this line from the centre of the knee on a long-leg radiograph provides the most accurate measure of coronal alignment. Malalignment causes abnormal forces which may lead to loosening after knee replacement. We report a series of 115 Denham knee replacements performed between 1976 and 1981 using the earliest design of components, inserted with intramedullary guide rods. Patients were assessed clinically and long-leg standing radiographs were taken before operation, soon after surgery and up to 12 years later. In two-thirds of the knees (68%) Maquet's line passed through the middle third of the prosthesis on postoperative films and the incidence of subsequent loosening was 3%. When Maquet's line was medial or lateral to this, an error of approximately +/- 3 degrees, the incidence of loosening at a median period of eight years was 24%. This difference is highly significant (p = 0.001). Accurate coronal alignment appears to be an important factor in prevention of loosening. Means of improving the accuracy of alignment and of measuring it on long-leg radiographs are discussed.

Adult

Survivorship analysis and confidence intervals. An assessment with reference to the Stanmore total knee replacement.

Survivorship analysis is a useful way of expressing the long-term results of joint replacement: it provides a means of comparing the life span of one type of prosthesis with another. However, such studies should include a full life-table and the confidence intervals for the survival rates at given times. At least 40 surviving prostheses are required to provide reliable results.

Confidence Intervals

The effects of improved blood glucose on growth hormone and cortisol secretion in insulin-dependent diabetes mellitus.

Growth hormone and cortisol secretion were studied in 25 patients with insulin-dependent diabetes before (Study 1) and 2 weeks after improved glucoregulation (Study 2). Blood samples for serum growth hormone (GH) and blood glucose determination were collected at hourly intervals whilst blood samples for cortisol and C-peptide were collected every 6 h during the 24-h period in Study 1 and Study 2. Glycaemic control was significantly improved in Study 2 compared to that in Study 1 (8.5 vs 13.3 mmol/l; P less than 0.001). With improved control, growth hormone levels rose by 21% (5.7 vs 4.7 mU/l; P less than 0.05). Throughout both study periods growth hormone levels were higher in patients with no residual C-peptide secretion (10 CpN patients) compared with patients with residual beta-cell function (15 CpP patients) (7.1 vs 3.2 mU/l in Study 1; 8.9 vs 4.2 mU/l in Study 2; P less than 0.001). Characteristic shapes of the 24-h blood glucose profile curves during both study periods were significantly different between the CpN and CpP group. Plasma cortisol decreased in both groups with improved metabolic control (P less than 0.001) but the observed different diurnal pattern did not change. These results demonstrate the importance of residual endogenous insulin secretion in determining growth hormone secretion in insulin-dependent diabetes and have important implications for glycaemic control and risk of microvascular complications.

Adult